Effects of AGI-1067 and probucol after percutaneous coronary interventions

Article

关键词: PREVENTING RESTENOSIS;    OXIDATIVE STRESS;    ANGIOPLASTY;    ATHEROSCLEROSIS;    ANTIOXIDANT;    HYPERCHOLESTEROLEMIA;    MULTIVITAMINS;    PROLONGATION;    EXPRESSION;    LDL;   

DOI  :  10.1161/01.CIR.0000047525.58618.3C

来源: SCIE

【 摘 要 】

Background-AGI-1067, a metabolically stable modification of probucol, is an equipotent antioxidant to probucol but is pharmacologically distinct. In a multicenter trial, we studied whether AGI-1067 reduces restenosis assessed by intravascular ultrasound (IVUS) after percutaneous coronary intervention (PCI) compared with placebo and probucol used as a positive control. Methods and Results-Two weeks before PCI, 305 patients were randomly assigned to 1 of 5 treatment groups: placebo, probucol 500 mg BID, or AGI-1067 70, 140, or 280 mg once daily. Patients were treated for 2 weeks before and 4 weeks after PCI. Baseline and 6-month follow-up IVUS were interpreted by a blinded core laboratory. Stents were used in 85% of patients. Luminal area at the PCI site at follow-up was 2.66 +/- 1.58 mm(2) for placebo, 3.69 +/- 2.69 mm(2) for probucol, 2.75 +/- 1.76 mm(2) for AGI-1067 70 mg, 3.17 +/- 2.26 mm(2) for AGI-1067 140 mg, and 3.3 6 +/- 2.12 mm(2) for AGI-1067 280 mg (P=0.02 for the dose-response relationship; P less than or equal to 0.05 for AGI-1067 280 mg and probucol versus placebo). There was a mean narrowing of 5.3 mm(3) of reference segment lumen in the placebo group and an enlargement in the AGI-1067 140- and 280-mg groups at follow-up (P=0.05 for 140 mg). An increase in QTc interval >60 ms occurred in 4.8% of placebo patients, 17.4% of probucol patients, and 4.8%, 2.4%, and 2.5% of patients in the AGI-1067 groups (P=0.02). Conclusions-AGI-1067 and probucol reduce restenosis after PCI. In contrast to probucol, AGI-1067 did not cause prolongation of the QTc interval and improved lumen dimensions of reference segments, suggestive of a direct effect on atherosclerosis.

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